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abatacept autoantibody

Hirokazu Sasaki, Hitoshi Kohsaka
Idiopathic inflammatory myopathies (IIMs) are heterogeneous disorders that affect the skeletal muscles. Polymyositis, dermatomyositis, and inclusion body myositis are major IIM subsets. Immune-mediated necrotizing myopathy became recognized as a potentially new IIM subset. Since the new classification criteria published by the International Myositis Classification Criteria Project have higher sensitivity and specificity for IIM classification and subclassification than the previous criteria, they should help precise diagnosis...
May 9, 2018: Modern Rheumatology
Diahann T S L Jansen, Paul Emery, Josef S Smolen, Rene Westhovens, Manuela Le Bars, Sean E Connolly, June Ye, René E M Toes, Tom W J Huizinga
Objective: To evaluate the effects of the T-cell costimulation blocker abatacept on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in early rheumatoid arthritis (RA), and associations between changes in serological status and clinical response. Methods: Post hoc analysis of the phase III AGREE study in methotrexate (MTX)-naïve patients with early RA and poor prognostic factors. Patients were randomised to abatacept (~10 mg/kg intravenously according to weight range) or placebo, plus MTX over 12 months followed by open-label abatacept plus MTX for 12 months...
2018: RMD Open
Aline Bozec, Yubin Luo, Cecilia Engdahl, Camille Figueiredo, Holger Bang, Georg Schett
BACKGROUND: The anti-inflammatory effect of abatacept is most pronounced in patients with high-titer autoantibodies (including anticitrullinated protein antibodies [ACPA] and rheumatoid factor [RF]). Considering that autoantibodies trigger inflammatory cytokine production by monocytes and that abatacept binds to monocytes, influencing their functional state, we hypothesized that abatacept may effectively inhibit the production of several different cytokines by ACPA- or RF-challenged monocytes...
February 7, 2018: Arthritis Research & Therapy
Somnath Bandyopadhyay, Sean E Connolly, Omar Jabado, June Ye, Sheila Kelly, Michael A Maldonado, Rene Westhovens, Peter Nash, Joan T Merrill, Robert M Townsend
Objective: To characterise patients with active SLE based on pretreatment gene expression-defined peripheral immune cell patterns and identify clusters enriched for potential responders to abatacept treatment. Methods: This post hoc analysis used baseline peripheral whole blood transcriptomic data from patients in a phase IIb trial of intravenous abatacept (~10 mg/kg/month). Cell-specific genes were used with a published deconvolution algorithm to identify immune cell proportions in patient samples, and unsupervised consensus clustering was generated...
2017: Lupus Science & Medicine
Marije K Verheul, Michel P M Vierboom, Bert A 't Hart, Rene E M Toes, Leendert A Trouw
BACKGROUND: Rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein (anti-CarP) antibodies are rheumatoid arthritis (RA)-associated autoantibodies. Besides their presence in human serum, anti-CarP antibodies have also been described in rodent models of arthritis, while ACPA are not consistently detectable. Data on these RA-associated autoantibodies in primates are not available. Therefore, we investigated the presence of RF, anti-CarP antibodies and ACPA in rhesus monkeys before and after collagen-induced arthritis immunizations...
November 2, 2017: Arthritis Research & Therapy
Shingo Nakayamada, Satoshi Kubo, Maiko Yoshikawa, Yusuke Miyazaki, Naoki Yunoue, Shigeru Iwata, Ippei Miyagawa, Shintaro Hirata, Kazuhisa Nakano, Kazuyoshi Saito, Yoshiya Tanaka
Objective: The aim of this study was to assess the therapeutic effects of biological DMARDs (bDMARDs) on the diversity of immune cell phenotypes in peripheral blood of patients with RA. Methods: Peripheral immune cell phenotypes were determined in 108 RA patients who were non-responsive to conventional DMARDs and 33 healthy control subjects by eight-colour flow cytometry. We also examined the correlation between the phenotypes and clinical findings and assessed the effects of 24-week treatment with bDMARDs...
January 1, 2018: Rheumatology
Josef S Smolen, Robert Landewé, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, Sofia Ramiro, Marieke Voshaar, Ronald van Vollenhoven, Daniel Aletaha, Martin Aringer, Maarten Boers, Chris D Buckley, Frank Buttgereit, Vivian Bykerk, Mario Cardiel, Bernard Combe, Maurizio Cutolo, Yvonne van Eijk-Hustings, Paul Emery, Axel Finckh, Cem Gabay, Juan Gomez-Reino, Laure Gossec, Jacques-Eric Gottenberg, Johanna M W Hazes, Tom Huizinga, Meghna Jani, Dmitry Karateev, Marios Kouloumas, Tore Kvien, Zhanguo Li, Xavier Mariette, Iain McInnes, Eduardo Mysler, Peter Nash, Karel Pavelka, Gyula Poór, Christophe Richez, Piet van Riel, Andrea Rubbert-Roth, Kenneth Saag, Jose da Silva, Tanja Stamm, Tsutomu Takeuchi, René Westhovens, Maarten de Wit, Désirée van der Heijde
Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib)...
June 2017: Annals of the Rheumatic Diseases
Rieke Alten, Hubert G Nüßlein, Xavier Mariette, Mauro Galeazzi, Hanns-Martin Lorenz, Alain Cantagrel, Melanie Chartier, Coralie Poncet, Christiane Rauch, Manuela Le Bars
OBJECTIVES: To determine the impact of baseline rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) status on the clinical efficacy of intravenous abatacept in biologic-naïve patients with rheumatoid arthritis (RA) enrolled in the real-world ACTION study. METHODS: Clinical outcomes (European League Against Rheumatism (EULAR) response, mean Clinical Disease Activity Index (CDAI) and Boolean remission) at 6 months were compared by baseline RF and anti-CCP status...
2017: RMD Open
Odilia B J Corneth, Gwenny M P Verstappen, Sandra M J Paulissen, Marjolein J W de Bruijn, Jasper Rip, Melanie Lukkes, Jan Piet van Hamburg, Erik Lubberts, Hendrika Bootsma, Frans G M Kroese, Rudi W Hendriks
OBJECTIVE: Bruton's tyrosine kinase (BTK) transmits crucial survival signals from the B cell receptor (BCR) in B cells. Pharmacologic BTK inhibition effectively diminishes disease symptoms in mouse models of autoimmunity; conversely, transgenic BTK overexpression induces systemic autoimmunity in mice. We undertook this study to investigate BTK expression and activity in human B cells in the context of autoimmune disease. METHODS: Using intracellular flow cytometry, we quantified BTK expression and phosphorylation in subsets of peripheral blood B cells from 30 patients with rheumatoid arthritis (RA), 26 patients with primary Sjögren's syndrome (SS), and matched healthy controls...
June 2017: Arthritis & Rheumatology
Carolin Wunderlich, Isabelle Oliviera, Camille P Figueiredo, Juergen Rech, Georg Schett
OBJECTIVE: To study whether stable treatment with DMARDs affects anti-CCP2 antibody levels in patients with rheumatoid arthritis. METHODS: In this longitudinal observational study 100 RA patients were followed for anti-CCP2 IgG antibody (U/L) and total IgG level (mg/dL) every 6 months for a total period of 2.5 years. All patients received stable DMARD treatment during this period. Five groups comprising each 20 patients were analyzed as follows: (1) methotrexate (MTX) alone, (2) tumor necrosis factor inhibitors (TNFi), (3) tocilizumab (TCZ), (4) rituximab (RTX), and (5) abatacept (ABA)...
June 2017: Seminars in Arthritis and Rheumatism
M Cutolo, A Sulli, C Pizzorni, S Paolino, V Smith
<p>Systemic sclerosis (SSc) is characterized by autoantibody production, progressive microvasculopathy, and aberrant extracellular matrix protein (ECM) synthesis in tissues. The disease presents two major clinical hallmarks: Raynaud's phenomenon (RP) and skin involvement, followed by varying prevalences of internal organ involvement. Despite significant advances in the management of certain organ-specific involvements and symptoms, the research for efficient markers and targets, to be used for an optimized treatment, is still ongoing...
January 2016: Acta Reumatológica Portuguesa
Maurizio Cutolo, Alberto Sulli, Carmen Pizzorni, Sabrina Paolino, Vanessa Smith
Systemic sclerosis (SSc) is characterized by autoantibody production, progressive microvasculopathy, and aberrant extracellular matrix protein (ECM) synthesis in tissues. The disease presents two major clinical hallmarks: Raynaud's phenomenon (RP) and skin involvement, followed by varying prevalences of internal organ involvement. Despite significant advances in the management of certain organ-specific involvements and symptoms, the research for efficient markers and targets, to be used for an optimized treatment, is still ongoing...
February 17, 2016: Acta Reumatológica Portuguesa
Silvia Piantoni, Enrico Colombo, Angela Tincani, Paolo Airò, Mirko Scarsi
The aim of this paper was to look for predictors of abatacept (ABA) therapy discontinuation in patients with rheumatoid arthritis (RA). Seventy-one RA patients treated with ABA were followed up. Demographical, clinical, and laboratory parameters of the patients, including peripheral blood T and B cell populations, different rheumatoid factor and anti-cyclic citrullinated peptide autoantibodies isotypes, and serum free light chains were evaluated. Comparing patients who discontinued ABA with those still in therapy we observed: a higher proportion of smokers (51...
April 2016: Clinical Rheumatology
Elisa Astorri, Alessandra Nerviani, Michele Bombardieri, Costantino Pitzalis
Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease affecting diarthrodial joints and extra-articular tissues; in the absence of an effective treatment, it is characterized by persistent symmetrical and erosive synovitis which leads to structural joint damage and lifelong disability. Several autoantibodies have been associated with RA such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). B cells have been shown to play a crucial role in the pathogenesis of RA by producing autoantibodies and promoting synovial inflammation through antigen presentation, T cells activation and cytokines production [1]...
2015: Current Pharmaceutical Design
Martin Aringer, Josef S Smolen
INTRODUCTION: The approval of belimumab and other advances in the field have narrowed the window for off-label use of biologicals in systemic lupus erythematosus (SLE). For consideration in severe and refractory disease, safety will play a major role. AREAS COVERED: We reviewed the literature on safety aspects of off-label biological use in SLE. Significant evidence is available for rituximab, whereas data on the off-label SLE therapy with other biologicals are much more limited...
February 2015: Expert Opinion on Drug Safety
Melanie Gruner, Anja Moncsek, Stefan Rödiger, Dagmar Kühnhardt, Eugen Feist, Ralf Stohwasser
BACKGROUND: PA28γ (also known as Ki, REG gamma, PMSE3), a member of the ubiquitin-and ATP-independent proteasome activator family 11S, has been proved to show proteasome-dependent and -independent effects on several proteins including tumor suppressor p53, cyclin-dependent kinase inhibitor p21 and steroid receptor co-activator 3 (SCR-3). Interestingly, PA28γ is overexpressed in pathological tissue of various cancers affecting e. g. breast, bowl and thyroids. Furthermore, anti-PA28γ autoantibodies have been linked to several autoimmune disorders...
2014: BMC Musculoskeletal Disorders
Sarah Novotny, Kedra Wallace, Florian Herse, Janae Moseley, Marie Darby, Judith Heath, James Gill, Gerd Wallukat, James N Martin, Ralf Dechend, Babbette LaMarca
Similar to preeclamptic women, hypertension in the chronic Reduced Uterine Perfusion Pressure Rat Model Of Preeclampsia (RUPP) is associated with increased CD4(+) T cells, cytokines, sFlt-1 and agonistic autoantibodies to the AngII receptor (AT1-AA). We examined the effect inhibition of T cell co-stimulation in RUPP rats treated with (A) (abatacept, 250 mg/kg, infused i.v. at gestation day 13), on hypertension and sFlt-1, TNF-α and AT1-AA. RUPP surgical procedure was performed on day 14. On day 19 MAP increased from 94+2 mmHg in Normal Pregnant (NP) to 123 ± 3 mmHg in RUPP control rats...
June 17, 2013: Journal of Hypertension: Open Access
Lazaros I Sakkas, Dimitrios P Bogdanos, Christina Katsiari, Chris D Platsoucas
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein/peptide autoantibodies (ACPAs). Citrulline derives from arginine by peptidyl arginine deiminases, and ACPAs are directed against different citrullinated antigens, including fibrinogen, fibronectin, α-enolase, collagen type II, histones. ACPAs are present in two thirds of RA patients have higher specificity than RF for RA, and are associated with joint radiographic damage and extra-articular manifestations and they are detected years before the onset clinical arthritis...
November 2014: Autoimmunity Reviews
K Takase, S C Horton, A Ganesha, S Das, A McHugh, P Emery, S Savic, M H Buch
OBJECTIVE: To determine whether serial ANA testing predicts biological disease modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in patients with rheumatoid arthritis (RA). METHODS: Serial autoantibody profiles, bDMARD treatment sequences and clinical data were collected from patients identified from our database that since 2005 received (i) a first bDMARD (tumour necrosis factor inhibitor (TNFi)) and (ii) tocilizumab and/or abatacept. RESULTS: Of over 1000 patients, 454 RA patients received a first TNFi...
September 2014: Annals of the Rheumatic Diseases
Carlo Selmi
The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes...
August 2014: Clinical Reviews in Allergy & Immunology
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